In rheumatoid arthritis, immune complexes localize to synovial tissues and other extravascular spaces. The majority of these immune complexes consist of IgG rheumatoid factor (IgG-RF) in the absence of exogenous antigens. Thus IgG-RF plays a central role in the immunopathogenesis of rheumatoid synovitis. The purposes of the present investigations are: 1) to study in detail the means by which IgG-RF forms immune complexes by self-association or reaction with serum IgG; 2) to determine to what extent the ability to make IgG-RF is genetically determined by immune response genes linked to Gm and/or HLA type; 3) to develop in vitro model systems in which IgG-RF production can be modulated through the administration of anti-idiotypic antibodies. The methodologies to be exploited involve radioimmunoassays for IgG-RF and its associated antigens, moving boundary sedimentation, the in vitro induction of RF synthesis by peripheral blood lymphocytes from rheumatoid and normal subjects, and the establishment of cloned RF producing human lymphocyte cell lines. The results should clarify our understanding of the pathogenesis of rheumatoid arthritis, and might suggest new modalities for the specific elimination of pathogenic autoantibodies in man.